Loss of Rb overrides the requirement for ERK activity for cell proliferation.
Date
2002-12ICR Author
Author
D'Abaco, GM
Hooper, S
Paterson, H
Marshall, CJ
Type
Journal Article
Metadata
Show full item recordAbstract
The Ras GTPase is a critical transducer of mitogenic signals ultimately leading to inactivation of the retinoblastoma (Rb) protein, but the molecular basis underlying Ras-dependent control of cell cycle kinetics remains to a great extent unknown. In an effort to further elucidate the role of Ras activation in cell cycle control, we have studied the role of the downstream Mek-ERK pathway in facilitating exit from the quiescent G0 state and passage through the G1/S transition. We have adopted a genetic approach in combination with U0126, an inhibitor of Mek activation to study the role of Mek in cell cycle progression. Here we report that whereas wild-type (Wt) mouse embryo fibroblasts (MEFs) depend on ERK activation to enter the cell cycle, Rb-deficient (Rb(-/-)) MEFs have a reduced requirement for ERK signalling. Indeed in the presence of U0126 we found that Rb-null MEFs can exit G0, make the G1/S transition and proliferate. Analysis of Rb-deficient tumour cell lines also revealed a reduced requirement for ERK signalling in asynchronous growth. We discuss the molecular mechanism that may underlie this escape from MAP kinase signalling.
Collections
Subject
Cells, Cultured
Tumor Cells, Cultured
Animals
Mice
Butadienes
Nitriles
Morpholines
Chromones
Cyclin-Dependent Kinases
Mitogen-Activated Protein Kinase Kinases
Mitogen-Activated Protein Kinases
Cyclins
Retinoblastoma Protein
Proto-Oncogene Proteins
Cell Division
MAP Kinase Signaling System
Gene Expression Regulation
Gene Deletion
Phosphorylation
Time Factors
Cyclin-Dependent Kinase 4
Phosphatidylinositol 3-Kinases
Research team
Oncogene
Language
eng
License start date
2002-12
Citation
Journal of cell science, 2002, 115 (Pt 23), pp. 4607 - 4616
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